This training program in environmental toxicology has supported 90 pre-doctoral and 66 postdoctoral trainees since its inception in 1975. During that same time period, 196 Ph.D. or Sc.D. degrees have been awarded to all students in the MIT toxicology program (trainees plus non-trainees). Of the pre-doctoral and postdoctoral graduates over the past 10 years, 52 out of 366 (14.2%) are in academic positions and 212 (58%) are in industry. The goal of this training program is to produce scientists professionally qualified to make original contributions to improved understanding of the impacts of environmental agents, especially hazardous chemicals, on human health. Trainees pick projects from the following areas: 1) analysis of genome-, proteome- and glycome-level responses to toxins and toxicants; 2) characterization of mutagenic responses to carcinogens as expressed hierarchically at the genome, cell, tissue, organism and population levels of organization; 3) construction of novel animal models for determining the effects of exposure of mammals to environmental agents; 4) investigation of intra-cellular kinase-mediated signaling cascades triggered in response to toxic agents, and during neoplastic transformation; 5) characterization of the chemistry underlying the reaction of toxins and toxicants with cellular macromolecules and other targets; 6) mechanistic assessment of the contribution of specific DNA adducts to genetic disease, and identification of the cellular defenses (e.g., DNA repair strategies) that protect against DNA damage; and 7) engineering-based design of novel model systems for evaluating responses to toxic agents. A central theme that has developed during the past five years, which links all thirteen research groups, is the interplay between environmental chemicals and infectious agents in human disease. Highlights of the program are a well-structured and constantly updated academic program taken by pre-doctoral students, a postdoctoral mentoring program, numerous toxicology-focused seminar programs and a large emphasis on research collaboration. More than 300 students apply for the pre-doctoral program in toxicology annually, allowing for good program selectivity. This proposal requests funding for seven pre-doctoral and six postdoctoral trainees. Relevance: This training program comes from an MIT department at the interface of science and engineering. Using and developing state-of-the-art technology, the trainees address cutting edge problems in environmental health. Our approaches involve measurement of risk, mining of complex biological data, modeling of systems exposed to environmental agents, and manipulation of systems to modulate risk.